March 16, 2011 -- An experimental gene therapy injected into the brains of patients with Parkinson's disease improved tremor, stiffness, and other movement symptoms and was safe with few side effects over six months of follow-up, a study shows.

The small study represents the first successful clinical trial comparing a gene-based treatment to sham treatment in Parkinson's or any neurologic disorder, says Michael Kaplitt, MD, PhD, who developed the gene therapy more than a decade ago. He hopes to market it if phase III trials confirm its effectiveness.

Kaplitt is vice president for research in the department of neurological surgery at Weill Cornell Medical College in New York City. He is a co-founder of the company Neurologix, which is developing the treatment and funded the study.

"For almost two decades we have recognized that gene therapy holds great promise for treating neurological diseases like Parkinson's and Alzheimer's," Kaplitt tells WebMD. "The problem has been translating that promise into reality."

Testing Gene Therapy

Gene therapy involves the use of genes to treat or prevent disease. The genes are transferred into targeted cells via viruses that have been rendered harmless.

While other gene-based treatments have shown promise for the treatment of Parkinson's disease in studies involving primates, the few that have made it to human trials have failed to show a clear benefit over sham treatments, Kaplitt says.

The 45 patients in the newly reported phase II study had moderate to advanced Parkinson's symptoms that were not adequately controlled with conventional treatments. They were treated at seven medical centers in the U.S.

Half got the gene therapy, which involved the infusion of genetic material directly into a key brain regions associated with motor function through tiny holes drilled in the brain.

The gene used in the treatment, glumatic acid decarboxylase (GAD), makes a chemical called GABA, which helps reduce the excessive firing of neurons that lead to Parkinson's symptoms.

Gene Therapy vs. Sham Treatment

In the sham portion of the study, neurosugeons drilled holes halfway through the patients' skulls and pretended to attempt to locate the exact location to place a catheter. This involved no small amount of acting, since the patients remained awake during the surgery in the belief that they were helping the surgeons locate the key brain regions.

The other patients in the study received the gene therapy delivered via catheter in a two-hour infusion. The researchers mimicked the infusion procedure in the sham-therapy patients.

Sixteen of the patients who got the gene therapy and 21 who got the sham surgery completed the study and were included in the analysis.

Over six months of follow-up, half of the gene therapy patients achieved significant improvement in symptoms, compared to 14% of the comparison patients.

Overall, the gene therapy patients had almost twice the improvement in motor scores as those who received the sham surgery: 23% vs. 12%.

Improvements in motor control were seen at one month and continued virtually unchanged throughout the six-month study, Kaplitt says.

The study was published online today in the journal Lancet Neurology.

Safety of Gene Therapy

Feigin is an associate professor of neurology and molecular medicine at The Feinstein Institute for Medical Research in Manhasset, N.Y. He has no ties to Neurologix and is not involved with developing the gene therapy.

Feigin tells WebMD that it is not yet clear if the treatment is more effective or is as effective as deep brain stimulation (DBS), which is the most widely used surgical treatment for Parkinson's disease.

"Even if this proves to have comparable or even near-comparable efficacy to DBS, I would think that it might still have a place in treatment," he says. "Most importantly, this study shows this kind of therapy can be done safely."